The highly organized structure of the articular cartilage extracellular matrix gives rise to the complex mechanical behavior of the tissue. The destruction of this organized structure in diseases such as osteoarthritis compromises the function of the tissue, leading to loss of mobility in the joint. Efforts to replace cartilage lost to arthritis are limited by the ability to reconstruct the functional heterogeneity of healthy articular cartilage in tissue implants. A critical first step to the development of materials that mimic this functional heterogeneity is the characterization of how the micron scale tissue structure affects the macroscopic mechanical response. Recently, considerable advances have been made towards characterizing spatial variations in the equilibrium mechanical response of articular cartilage under compression. This proposal builds on this work and shows how to extend such measurements to address the heterogeneous dynamic response of articular cartilage tissue under shear. Moreover, recent technological advances in the manufacture of confocal microscopes are allowing for rapid in situ imaging of the three dimensional material structure. By combining this imaging capability with force measurement and image analysis tools it is now possible to make three dimensional correlation maps between the local tissue mechanical and structural responses and the applied macroscopic shear stress. The experiments proposed will take full advantage of these capabilities to investigate the effects of the applied strain rate, strain amplitude, and tissue compression on the material response at the macroscopic and microscopic levels. The detailed characterization of the cartilage shear properties obtained from these experiments will lead to a more thorough understanding of function in normal tissue, enable more effective diagnosis and monitoring of disease, and provide benchmarks and design input for efforts to replace or regenerate tissue. As such, these investigations are critical both for advancing the state of the art methods and technologies available to researchers and providing valuable information on the properties of this ubiquitous and important tissue. [unreadable] [unreadable] [unreadable]